B7-H4 antibodies and methods of use thereof
Inventors
Langermann, Solomon • FLIES, DALLAS BENJAMIN • Liu, Linda
Assignees
Publication Number
US-12286478-B2
Publication Date
2025-04-29
Expiration Date
2039-01-23
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Abstract
Compositions and methods of use thereof for modulating B7-H4 are provided. For example, immunomodulatory agents are provided that reduce B7-H4 expression, ligand binding, crosslinking, negative signaling, or a combination thereof. Such agents can be used to increase an immune response in a subject in need thereof. Immunomodulatory agents are also provided that increase B7-H4 expression, ligand binding, crosslinking, negative signaling, or a combination thereof. Such agents can be used to reduce an immune response in a subject in need thereof.
Core Innovation
This invention provides compositions and methods for modulating B7-H4 signal transduction using immunomodulatory agents. These agents can either reduce or increase B7-H4 expression, ligand binding, crosslinking, and negative signaling, thus enabling targeted manipulation of immune responses in subjects in need thereof. Immunomodulatory agents described include antibodies or antigen binding fragments, fusion proteins, aptamers, or other agents that specifically bind B7-H4 and modulate its signal transduction pathway.
The problem addressed by the invention stems from the role of B7-H4 as an immune checkpoint that inhibits T-cell function, and is upregulated in various tumors and tumor-associated macrophages, contributing to tumor growth and immune evasion. High B7-H4 expression is correlated with poor clinical outcomes and adverse features in cancer, making B7-H4 a significant target for immunotherapy. Existing approaches have limitations, and there is a need for new immunomodulators that specifically target B7-H4 to enhance or suppress immune functions.
The core innovation includes anti-B7-H4 antibodies with defined sequences and variants, nucleic acids encoding these antibodies, and pharmaceutical compositions comprising these agents. The antibodies and related compositions can selectively increase or decrease immune responses by blocking or enhancing B7-H4-mediated signaling in diseases characterized by aberrant immune suppression or activation. Methods of use for treating cancer, infections, inflammation, and autoimmune disorders through administration of the disclosed agents are described, along with detailed compositions and delivery strategies.
Claims Coverage
The independent claims set forth several inventive features, focusing on specific anti-B7-H4 antibodies and their uses, compositions, vectors, host cells, and related methods for modulating immune response.
Anti-B7-H4 antibody with specific light and heavy chain sequences
An anti-B7-H4 antibody or antigen binding fragment thereof comprising: - A light chain with an amino acid sequence according to SEQ ID NO: 63 (humanized B1H10 light chain variant). - A heavy chain with an amino acid sequence according to SEQ ID NO: 81 (humanized mutant B1H10 heavy chain variant). This structure precisely defines the antibody by its amino acid sequences.
Pharmaceutical composition containing anti-B7-H4 antibody to increase immune response
A pharmaceutical composition comprising an effective amount of an immunomodulatory agent that reduces B7-H4 expression, ligand binding, crosslinking, negative signaling, or a combination thereof, consisting of the above-defined anti-B7-H4 antibody or antigen binding fragment, for the purpose of increasing an immune response in a subject in need thereof.
Vector encoding anti-B7-H4 antibody or fragment
A vector comprising a nucleic acid sequence or nucleic acid sequences encoding the anti-B7-H4 antibody or antigen binding fragment as defined by the specific light and heavy chain sequences.
Host cell comprising antibody-encoding sequence or vector
A host cell comprising a nucleic acid sequence, or a vector encoding the anti-B7-H4 antibody or antigen binding fragment as defined by the previous claims.
Method of increasing immune response by administering antibody composition
A method of increasing an immune response in a subject in need thereof by administering to the subject the pharmaceutical composition containing the anti-B7-H4 antibody described above. This includes diseases such as cancer characterized by increased B7-H4 expression and the possibility of contemporaneous administration with a vaccine or a second therapeutic agent.
Pharmaceutical composition to decrease immune response using anti-B7-H4 antibody
A pharmaceutical composition comprising an effective amount of an immunomodulatory agent that increases B7-H4 expression, ligand binding, crosslinking, negative signaling, or a combination thereof, selected from the group consisting of the aforementioned anti-B7-H4 antibody or antigen, to decrease an immune response in a subject in need thereof.
Method of reducing immune response via anti-B7-H4 antibody composition
A method of reducing an immune response in a subject in need thereof by administering the pharmaceutical composition that increases B7-H4 activity. The method is applicable for treating inflammation or autoimmune disorders, including rheumatoid arthritis or conditions characterized by reduced B7-H4 expression, and can be combined with a second therapeutic agent.
The claims establish protection for anti-B7-H4 antibodies with explicit sequence identities, pharmaceutical compositions using these antibodies to modulate immune responses, vectors and host cells for their production, and the therapeutic methods for their clinical use in treating diseases by increasing or decreasing immune responses.
Stated Advantages
The disclosed compositions allow for targeted modulation of B7-H4 signaling to either enhance or suppress immune responses in a subject, supporting versatile therapeutic strategies.
The immunomodulatory agents can be used to treat a wide range of diseases, including cancer, infections, inflammation, and autoimmune disorders, by specifically increasing or decreasing the immune response as required.
The invention provides pharmaceutical compositions, vectors, and host cells for efficient delivery and production of anti-B7-H4 antibodies with defined sequences, facilitating precise therapeutic applications.
Documented Applications
Treatment of cancer, including but not limited to ovarian, breast, lung, thyroid, gastrointestinal cancer, acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), endometrial cancer, brain cancer, head and neck cancer, pancreatic cancer, and bladder cancer.
Treatment of infectious diseases by expanding neutrophils and/or increasing innate immunity in subjects with infections caused by bacteria, viruses, fungi, or parasites as explicitly enumerated in the patent.
Treatment of inflammation or autoimmune disorders, including rheumatoid arthritis and other autoimmune diseases and inflammatory conditions documented in the disclosure.
Use in combination therapies, such as in conjunction with vaccines, chemotherapeutic agents, immunomodulators (e.g., PD-1 antagonists), potentiating agents, and anti-inflammatory treatments as described for personalized or synergistic medical regimens.
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